Severe phenotype in infantile facioscapulohumeral muscular dystrophy

Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, United Kingdom.
Neuromuscular Disorders (Impact Factor: 2.64). 11/2006; 16(9-10):553-8. DOI: 10.1016/j.nmd.2006.06.008
Source: PubMed


While much is known about the clinical course of adult FSHD, the third most common inherited muscular dystrophy, data on the "infantile phenotype" and especially on the progression of the disease in children are limited. We have followed a cohort of 7 patients with infantile FSHD for 9-25 years and here report the clinical and genetic findings in this group. Infantile FSHD is relatively rare, amounting to 4% of all of our FSHD patients. Despite some variability in the progression, infantile FSHD has a more consistent phenotype than adult FSHD. Although they had normal motor milestones, all patients showed facial weakness from early childhood, and subsequently were severely affected with rapid progression of the disease, marked muscular wasting, weakness, and hyperlordosis. None of the patients have shown signs of nocturnal hypoventilation or cardiomyopathy so far. No correlation was found between sex and the severity of phenotype whereas all but one patient had very short fragment sizes of the D4Z4 repeat. Only two patients had a de novo mutation: 3 patients inherited the mutation from a parent with somatic mosaicism, and one was inherited from a parent with classical adult FSHD. One patient was unusual in having one allele inherited from his father who showed somatic mosaicism and one allele with an additional de novo mutation. We conclude that infantile FSHD is a severe and rapidly progressive disease, and this needs to be taken into account in the advice given to patients diagnosed in early childhood. However, our data also suggest that the risk to an individual with classical FSHD of having a child with the infantile form is low.

14 Reads
  • Source
    • "A rough reverse correlation between clinical severity and the size of D4Z4 repeat has also been reported [6] [7]. Early-onset FSHD patients usually have small D4Z4 fragment size and become wheelchair-bound before adulthood [8] [9]. Muscle imaging has been shown to disclose different muscle involvement in various types of muscular dystrophy that may be difficult to detect clinically [10] [11] [12] [13] [14] [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to evaluate muscle involvement pattern and correlate the lesions on muscle imaging with clinical features and D4Z4 fragment size in 24 patients with facioscapulohumeral muscular dystrophy (FSHD). The grading of the muscle image detected by computed tomography (CT) was based on a four-point semi-quantitative visual scale. On muscle CT, the most affected muscle was trapezium, followed by hamstrings. CT image identified hamstrings involvement rather than shoulder-girdle in clinically asymptomatic subjects. CT image also showed that axial muscle was affected in one-third of patients which appeared even earlier than clinical manifestation. Strong correlations between CT findings, serum creatine kinase level and clinical severity scores were also found. Asymmetric involvement was more evident on CT image than it identified in manual muscle strength testing. Inverse correlation between CT grade and D4Z4 fragment size was clearly demonstrated. These findings suggest muscle CT will be helpful for the process of early intervention in FSHD, even in subjects in a preclinical status.
    Neuromuscular Disorders 12/2011; 22(4):331-8. DOI:10.1016/j.nmd.2011.10.018 · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have fabricated the square-shaped double-clad Nd-doped fiber for testing its potential as power amplifier. The output power of 3.3 W is obtained with the optical-to-optical conversion efficiency of 47%. The efficiency is expected to be further improved by the codopant compositions
    Lasers and Electro-Optics, 1998. CLEO 98. Technical Digest. Summaries of papers presented at the Conference on; 06/1998
  • [Show abstract] [Hide abstract]
    ABSTRACT: A variety of different pathologies result in disease phenotypes that are summarized as neuromuscular diseases because they share commonalty in their clinical consequences for the patient: a progressive weakening of the skeletal muscles. Distinct caution and appropriate changes to the anesthetic plan are advised when care is provided during the perioperative period. The choice of anesthetic technique, anesthetic drugs, and neuromuscular blockade always depends on the type of neuromuscular disease and the surgical procedure planned. A clear diagnosis of the underlying disease and sufficient knowledge and understanding of the pathophysiology are of paramount importance to the practitioner and guide optimal perioperative management of affected patients.
    Anesthesiology Clinics 10/2007; 25(3):483-509, viii-ix. DOI:10.1016/j.anclin.2007.05.005
Show more

Similar Publications